Certain polycyclic gem substituted ketones having mixed pendant groups have been found to enhance the stimulus-induced release of neurotransmitters in brain tissues and, thus, to improve processes involving learning memorization of active avoidance tasks. Compounds of interest have the formula: EQU R.sub.1 --CH.sub.2 --Q--R.sub.5
wherein:
Q is ##STR2##
R.sub.1 is a heterocyclic aromatic moiety such as a 4-, 3-, or 2-pyridyl, pyrimidyl, pyrazinyl, or fluoro-4-pyridyl group;
R.sub.2 and R.sub.3 are independently H, F, Cl, Br, NO.sub.2, OH, R.sub.4, OR.sub.4, CO.sub.2 R.sub.4, COR.sub.4, CONH.sub.2, CONHR.sub.4, CON(R.sub.4)(R.sub.4 '), S(O).sub.m --R.sub.4, NH.sub.2, CF.sub.3, NHR.sub.4, or N(R.sub.4)(R.sub.4 ');
R.sub.4 and R.sub.4 ' are independently H, alkyl having from about 1 to about 4 carbon atoms, CH.sub.2 Phe-W, or Phe-W;
Phe is a phenyl group;
R.sub.5 is --(CH.sub.2).sub.n --Y or --OCOR.sub.4 ;
Y is H, OH, NH.sub.2, NHR.sub.4, N(R.sub.4),(R.sub.4 '), NHCOR.sub.4, NHCO.sub.2 R.sub.4, NHS(O).sub.2 R.sub.4, F, Cl, Br, OR.sub.4, S(O).sub.m R.sub.4, CO.sub.2 H, CO.sub.2 R.sub.4, CN, CON(R.sub.4)(R.sub.4 '), CONHR.sub.4, CONH.sub.2, COR.sub.4, Phe, Phe-W, --C.tbd.CCO.sub.2 R.sub.4, --CH.dbd.CHR.sub.4, --C.tbd.CR.sub.4, or a heterocyclic aromatic moiety such as a 4-, 3-, or 2-pyridyl, pyrimidyl, pyrazinyl, or fluoro-4-pyridyl group;
W is F, Cl, Br, R.sub.4, OR , NO.sub.2, NH.sub.2, NHR.sub.4, N(R.sub.4)(R.sub.4 '), CN, or S(O).sub.m --R.sub.4 ;
m is 0, 1, or 2; and
n is about 1-7.
A number of proposed syntheses for these compounds employ polycyclic ketones having formulas (1)-(3) as starting materials. ##STR3## Certain of the polycyclic ketones are commercially available. For example, 4,5-diazafluoren-9-one can be obtained from GFS Chemicals (Columbus, Ohio). To date, however, it generally has not been possible to synthesize ketones of this type except through low-yielding procedures. For example, Dickeson, et al., Aust. J. Chem., 1970, 23, 1023, disclosed a four-step synthesis of 4,5-diazafluoren-9-one (8) from phenanthroline (4) in 15% overall yield. The synthesis involved the reduction of 5-nitro-1,10-phenanthroline (5) to 5-amino-1,10-phenanthroline (6), which was oxidized to 1,10-phenanthroline-5,6-quinone (7). Quinone (7) was treated with aqueous alkali to give the ketone (8). ##STR4##
Inglett and Smith, J. Am. Chem. Soc., 1950, 72, 842 disclosed synthesizing 4,5-diazafluoren-9-one (8) in less than 10% overall yield by treating the nitration filtrate of phenanthroline (4) with aqueous sodium hydroxide solution. Earlier, Smith, et al., J. Org. Chem., 1947, 12, 781, had reported that the nitration filtrate contains 1,10-phenanthroline-5,6-quinone (7).
Kloc, et al., Journal f. Prakt. Chemie., 1977, Band 319, Heft 6, 959, reported a one-step synthesis of 4,5-diazafluoren-9-one (8) in about 55% yield by oxidizing 1,10-phenanthroline (4) in alkaline permanganate. However, Echard, et al., Aust. J. Chem., 1973, 26, 2727, reported 2,2'-dipyrido-3,3'-dicarboxylic acid as the major product of this reaction.
Accordingly, there exists a need in the art for more efficient and effective methods for synthesizing polycyclic ketones such as those having formulas (1)-(3).